Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype

Area of Science:

• Neuroscience
• Clinical Neurology
• Pharmacology

Background:

• Progressive multiple sclerosis (MS) encompasses primary progressive MS (PPMS) and secondary progressive MS (SPMS) forms, both characterized by continuous disability progression.
• The differential treatment response between PPMS and SPMS phenotypes remains largely unexplored.

Purpose of the Study:

• To investigate whether the treatment effect of ibudilast on the rate of brain atrophy differs between PPMS and SPMS patients.
• To analyze the impact of MS phenotype on treatment efficacy in a phase 2 clinical trial.

Main Methods:

• The SPRINT-MS trial was a 96-week, randomized, placebo-controlled study involving 134 PPMS and 121 SPMS patients.
• A three-way interaction linear-mixed model was employed to assess the effect of time, ibudilast treatment, and MS phenotype (PPMS vs. SPMS) on brain atrophy, measured by brain parenchymal fraction (BPF).
• Adjustments were made for baseline demographics, disease measures, and brain size.

Main Results:

• A significant three-way interaction indicated that the treatment effect of ibudilast varied by MS phenotype (P < 0.06).
• The overall treatment benefit of ibudilast was predominantly observed in PPMS patients (P < 0.01), with no significant effect in SPMS patients (P = 0.97).
• Faster brain atrophy progression in the PPMS placebo group compared to the SPMS placebo group (P < 0.02) may explain this differential treatment response.

Conclusions:

• The previously reported overall efficacy of ibudilast in reducing brain atrophy in progressive MS is primarily driven by its effect in PPMS patients.
• The observed difference in treatment response may be partly attributed to the higher rate of brain atrophy progression in the PPMS subgroup receiving placebo.